Objective:To investigate the effects of ascites grading and the application of non-selective beta-blockers (NSBBs) on the 1-year prognosis of acute-on-chronic liver failure (ACLF).Methods:1 386 ascitic cases with ACLF were graded and followed up for one year. The 1-year prognostic effect of ascites grade and NSBBs was analyzed on ACLF by the Kaplan Meier Log-rank test, Cox stepwise regression, and multivariate regression.The t-test, Mann-Whitney U, or Kruskal-Wallis test were used for intergroup comparison of measurement data. The χ2 test was used for intergroup comparison of numerical data. Results:The incidence rate of ascites at admission was 77.56% in 1 386 ACLF cases. The Log-rank (Mantel-Cox) of the 1-year survival curve test for 1 386 ACLF patients with ascites grade was 21.384, P<0.01. Multivariate regression and Cox stepwise regression analysis showed that ascites grade, age, gastrointestinal bleeding, pulmonary infection, acute kidney injury, prothrombin activity (PTA), urea, MELD-Na score, and the use of NSBBs were closely related to the 1-year prognosis of ACLF. The log rank (Mantel-Cox) of NSBBs treatment in the grade 2/3 ascites group was 6.113, P=0.013, and the difference was statistically significant, suggesting that NSBBs treatment can help improve the 1-year survival rate in ACLF patients with grade 2 and 3 ascites. Conclusions:Ascites grading and the use of NSBBs affect the prognostic factor of ACLF at one year. NSBBs may be beneficial for the long-term prognosis of ACLF, and treatment can be continued in patients who have already received NSBBs prior to the onset of ACLF.

Ascites is the most common complication in the decompensated stage of cirrhosis, with approximately 5% to 10% progressing to refractory ascites (RA). The complex pathogenesis, difficult treatment, and poor prognosis are major challenges and difficulties in the clinical treatment of RA. Tolvaptan (TLV) is a kind of novel non-peptide, selective arginine vasopressin V2 receptor antagonist that can inhibit renal water reabsorption, promote free water excretion, and increase blood sodium levels, providing a new clinical option for the treatment of cirrhotic RA. This paper briefly summarizes the mechanism of action of TLV and introduces its effectiveness, safety, and predictive factors response in order to provide a reference for clinical application in the treatment of cirrhotic RA.

Objective:To explore the clinical and genetic characteristics and follow-up status of pediatric patients with hepatic glycogen storage disease in order to further improve the prognosis.Methods:The clinical data of hospitalized children diagnosed with hepatic glycogen storage disease in the Department of Gastroenterology at the Children's Hospital of Capital Institute of Pediatrics from January 2010 to April 2023 were collected and retrospectively analyzed. The results of laboratory examination and gene sequencing were analyzed, and the number of cases that exceeded three (n) were grouped according to the genetic results: Group 1 was type Ⅰ ( n=8), Group 2 was type Ⅲ ( n=5), and Group 3 was type Ⅸa ( n=8).The growth, development and prognosis of the children were followed up. The related clinical characteristics of pediatric hepatic glycogen storage disease were summarized. Results:Twenty-five pediatric patients with hepatic glycogen storage disease were enrolled in this study, with fifteen males and ten females. The mean age of diagnosis was (29.1±13.5) months. There were twelve cases (48%) accompanied with varying degrees of hypoglycemia, and two cases (8%) with severe hypoglycemia.There were nineteen cases with stature retardation (76%), four cases with anemia (16%), three cases with proteinuria (12%), and one case with cholestasis (4%).The genetic results showed that there were four cases of type Ⅰa (16%), four cases of type Ⅰb (16%), one case of type Ⅱ (4%), five cases of type Ⅲ (20%), two cases of type Ⅳ (8%), one case of type Ⅵ (4%), and eight cases of type Ⅸ (32%).The three subgroups analysis showed that there were significant statistical differences in uric acid and triglycerides among the three groups ( P<0.05), while there were no statistical significant differences in transaminase levels, fasting blood glucose, lactate, cholesterol, and low-density lipoprotein levels ( P>0.05). The height-for-age Z scores of the three groups were -2.86±1.62, -1.46±1.06, and -1.83±0.98, respectively. The growth and development of groups 2 and 3 were significantly improved compared with group 1 ( P<0.05), with Z scores of -2.28±1.07, 0.20±1.54, and 0.10±1.44 after at least one year of follow-up. All pediatric patients with type Ⅸa had discontinued using raw corn starch after more than one year of follow-up and their transaminases had returned to normal. Four pediatric patients with type Ia were orally administered raw corn starch on a regular basis, and the aminotransferases, uric acid, and lactate were normal, with hypoglycemia being monitored. Among the four cases with type Ⅰb, one had recurrent respiratory tract and intestinal infections, two were combined with Crohn's disease, and one was monitored for hypoglycemia. In four cases of type Ⅲ, raw corn starch was discontinued, and a high-protein, low-carbohydrate diet was adopted, with the exception of the presence of high creatine kinase and normal aminotransferase. Liver failure resulted in the death of one type Ⅵ case, while two were type Ⅳ cases; one died, and one case recently had slightly elevated aminotransferase. Conclusion:When pediatric patients exhibit manifestations such as hepatomegaly, elevated transaminases, fasting hypoglycemia, and delayed growth and development, it is necessary to be alert to hepatic glycogen storage disease. Clinical manifestations and biochemical indicators combined with genetic testing are helpful for the diagnosis of hepatic glycogen storage disease. Simultaneously, targeted nutritional management should be carried out according to the metabolic characteristics of different subtypes, with attention on growth and development status.

Objective:To investigate the correlation between the expression of the immunohistochemical marker cytokeratin (CK)-19 and the clinical characteristics and prognosis of dual-phenotype hepatocellular carcinoma (DPHCC).Methods:The data of patients diagnosed with hepatocellular carcinoma (HCC) who underwent surgical resection were collected. DPHCC cases were screened by immunohistochemistry, followed up, and grouped. The correlation between the expression of the immunohistochemical marker CK-19 and the clinical pathological characteristics and prognosis of DPHCC was analyzed by statistical methods. The enumeration data were compared using the χ2 test or Fisher's exact probability method between groups. Results:The expression of CK19 was significantly correlated with factors such as the tumor size, histological grade, liver tissue cirrhosis surroundings, microvascular invasion (MVI), and serum carbohydrate antigen 199 (CA-199) levels in DPHCC, and the differences were statistically significant ( P<0.05). There was no significant correlation between the expression of CK19 and the gender, age, tumor necrosis, multiple lesions, liver capsule invasion, serum alpha-fetoprotein (AFP), and immunohistochemical CK7 and mucin 1 (MUC-1) in DPHCC patients, and the differences were not statistically significant ( P>0.05). The results of univariate analysis showed that immunohistochemical CK19 expression, MVI, number of lesions, tumor necrosis, tumor differentiation degree, serum AFP, and carbohydrate antigen 199 levels were related factors affecting the prognosis in DPHCC patients ( P<0.05); while gender, age, capsule invasion, tumor size, and expression of immunohistochemical markers (vascular endothelial growth factor, CK7, MUC-1) were not significantly correlated with the prognosis in DPHCC patients ( P>0.05). The results of multivariate analysis showed that tumor necrosis ( P=0.042, 95% CI: 1.031-5.501) and serum AFP levels were independent risk factors affecting the prognosis in DPHCC patients ( P<0.001, 95% CI: 2.581-24.075). Conclusions:The expression of CK19 is closely related to the prognosis of patients with DPHCC. Patients with high CK19 expression have faster disease progression than those with low CK19 expression. Furthermore, the overall survival rate of patients with high CK19 expression is significantly lower than that of patients with low CK19 expression, which is a risk factor for poor prognosis in patients with DPHCC.

Objective:To experimentally validate clinical samples, analyze the mRNA expression of the FYVE domain containing phosphatidylinositol 3-phosphate 5 kinase ( PIKFYVE) gene, and its clinical significance based on the Cancer Genome Atlas (TCGA) database in hepatocellular carcinoma (HCC). Methods:Data information on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of non-tumorous liver tissues) were collected based on the TCGA database. Cox regression analysis and the Kaplan-Meier method were used to analyze the relationship between mRNA expression of the PIKFYVE gene and the clinical characteristics as well as survival prognosis in patients with HCC. The relationship between the PIKFYVE gene and immune cell infiltration was examined by correlation analysis with 24 kinds of immune cells. In addition, the mRNA expression level of the PIKFYVE gene and RAC-alpha serine/threonine-protein kinase ( AKT1), phosphatase and tensin homolog ( PTEN), protein kinase C alpha ( PRKCA), inositol polyphosphate-5-phosphatase ( INPP5D), phosphoinositide-3-kinase regulatory subunit 1 ( PIK3R1), inositol polyphosphate 4-phosphatase type II ( INPP4B) and phospholipase C beta 4 ( PLCB4) gene correlations were analyzed in HCC tissues. At the same time, paraffin sections of highly differentiated, moderately differentiated, poorly differentiated, and non-tumor liver tissues from patients with HCC were collected from the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University. The histopathological observation was performed by HE staining. Immunohistochemistry was used to verify the expression levels of the PIKFYVE and Ki67 proteins in each clinical sample. The t-test was used for intergroup comparison of continuous data. The χ2 test and Wilcoxon rank sum test were used for intergroup comparison of enumeration data. The Kaplan-Meier method was used for survival analysis. Results:The expression level of the PIKFYVE gene was higher in the HCC tumor than that in normal liver tissue ( P<0.01). The overall survival time of patients was significantly longer in the low expression group than that in the high expression group ( HR=1.57, 95% CI: 1.10～2.25, P=0.014). The results of univariate Cox regression analysis showed that tumor stage, pathological grade, tumor status, residual tumor, and PIKFYVE expression level all had an effect on OS ( P<0.05). The PIKFYVE prognostic risk model had a proportionate score of HR=1.533 (95% CI: 1.077～2.181, P=0.018). Multivariate Cox risk regression analysis showed that the PIKFYVE prognostic risk model had a proportionate score of HR=1.481 (95% CI: 0.886～2.476, P=0.134) and an area under the receiver operating characteristic curve of 0.559, indicating that it had predictive value for survival prediction. The results of the correlation analysis showed that the expression level of PIKFYVE was strongly correlated with immune cell infiltration and TP53 ( P<0.01). The results of immunohistochemical staining showed that the expression level of PIKFYVE was significantly higher in HCC tissue samples than that in non-tumor liver tissues ( P<0.01), and was negatively correlated with the degree of differentiation. Conclusion:PIKFYVE, as an independent risk factor, is expected to be developed into a biomarker for clinical diagnosis, offering a reference for novel therapeutic agents in HCC.

Primary sclerosing cholangitis (PSC) is a type of chronic idiopathic liver disease characterized by bile duct inflammation and concentric fibrosis. Currently, no drug therapy can change the natural progression of PSC. The mechanism by which PSC is accompanied by the occurrence of inflammatory bowel disease (IBD) is still unclear. Oral antibiotic therapy with vancomycin being the most widely used has been shown to be effective for PSC combined with IBD. This paper analyzes case reports and clinical studies on the use of vancomycin in PSC, with the aim of providing a reference for clinical therapy and in-depth exploration of novel therapeutic directions.

Objective:To investigate the interventional effects of the Fuzheng Huayu (FZHY) formula and its partial mechanistic role on cholestatic liver fibrosis in mice.Methods:Mdr2 gene knockout (Mdr2－/ －) mice were randomly divided into a model group, FZHY group, and Obeticholic acid group. Wild-type C57BL/6J mice of the same age served as the control group. Mdr2－/ －mice were given the corresponding drugs starting from the first day of 9 weeks of age by oral gavage in each group. The control and model groups were administered 0.3% sodium carboxymethylcellulose by oral gavage and were sacrificed at 12 weeks of age for specimen collection. High-speed biochemistry analyzer was used to detect serum alkaline phosphatase and alanine aminotransferase activity in mice. Hematoxylin-eosin staining and Sirius red staining were used to observe pathological changes in liver tissues. Hydroxyproline content was measured to assess collagen in liver tissues. Immunohistochemical staining, Western blotting, and real-time fluorescence quantitative PCR were used to detect the expression of fibrosis markers Col-I and alpha-smooth muscle actin in liver tissues. The expressional condition of cholangiocyte response markers Epcam, CK7, CK19, as well as Pcna, Mki67, and Ccnd1, inflammatory related factors Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4, phosphorylated peroxisome proliferator-activated receptor alpha (PPARα) and nuclear factor kappa-B (NF-κB) were determined. Comparative analysis among multiple groups was performed using one-way ANOVA. The LSD method was used for comparisons between groups. Two-tailed statistical tests were used.Results:Compared with wild-type mice, Mdr2 －/ － mice had a significant increase in serum alanine aminotransferase and alkaline phosphatase activity ( P<0.001). The percentage of Sirius red-positive staining areas and hydroxyproline content in liver tissues was significantly increased ( P<0.01). The expression of Col-I, α-smooth muscle actin, Epcam, CK7, CK19, Pcna, Mki67, and Ccnd1, and the expression of Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4 were significantly increased ( P<0.01); however, both FZHY and Obeticholic acid significantly reversed the increases in these indicators ( P<0.05; P<0.01). Further results showed that compared to wild-type mice, the expression of PPARα was significantly reduced in liver tissues of Mdr2 －/ － mice, while NF-κB was significantly enhanced ( P<0.01). In contrast, compared to Mdr2-/- mice, the expression of PPARα in the liver tissues of FZHY group mice was significantly increased ( P<0.05), while NF-κB was significantly inhibited ( P<0.05). Conclusion:FZHY can significantly improve liver fibrosis, cholangiocyte response, and inflammation in Mdr2 －/ － mice with spontaneously occurring cholestatic liver fibrosis, and its mechanistic role is related to the regulation of the PPARα/NF-κB pathway.

Objective:To analyze the clinical and genetic features of four children with pediatric acute liver failure (PALF) caused by neuroblastoma-amplified sequence ( NBAS) gene variant, as well as the correlation between clinical phenotype and genotype. Methods:The clinical data and genetic test results of four children with NBAS gene variants admitted to the Department of Gastroenterology, Children's Hospital Affiliated to Zhejiang University School of Medicine from August 2015 to June 2023 mainly presenting with pediatric acute liver failure (PALF) were retrospectively analyzed. The relevant literature from January 2015 to May 2024 was retrieved using the Chinese and English keywords " NBAS," "neuroblastoma amplified sequence," "SOPH," "short stature with optic nerve atrophy and Pelger Hu?t anomaly," "liver failure," and "neuroblastoma amplified sequence" indexed in the CNKI database, Wanfang Data Knowledge Service Platform, and PubMed database. The clinical features and gene mutation characteristics of domestic patients were summarized. Results:The age at which the initial PALF attack occurred in the four children varied from eight months to three years and seven months. All patients developed PALF within 1-2 days after the onset of fever, with symptoms such as vomiting, convulsions, and mental depression or confusion, accompanied by a sharp increase in transaminases, elevated bilirubin and blood ammonia, hyperlactatemia, and hepatomegaly. The PALF gradually improved, and three pediatric patients showed extrahepatic manifestations following antipyretic, fluid replacement, and other symptomatic supportive treatment. Long-term follow-up showed that active temperature control and symptomatic therapy reduced the recurrence of PALF. Genetic testing identified eight kinds of NBAS gene variants sites. Family testing validated compound heterozygous variants, which included four missense variants, one nonsense variants, and three frameshift mutations. A literature study revealed that out of 51 Chinese patients with NBAS gene variants, 98.0% (50/51) had liver involvement, and 37 cases showed PALF. A total of 61 mutation sites were identified, with c.3596G>A (45.1%, 23/51) as a hotspot variants. Conclusions:PALF caused by NBAS gene variant has obvious clinical and genetic characteristics, and there is a correlation between genotype and clinical phenotype. The c.3596G>A variant site is a hotspot mutation in China and is strongly correlated with the liver failure phenotype.

Objective:To investigate the curative effect and possible mechanism of rifaximin treatment on monocrotaline-induced hepatic sinusoidal obstruction syndrome (HSOS) in mice.Methods:Twenty-four male C57BL/6J mice were divided into three groups and treated with solvent control, monocrotaline, and rifaximin, respectively. The histopathological changes of the liver and intestine were observed by hematoxylin-eosin staining. The differences were compared in liver parameters, serum liver enzymes, inflammatory factors, apoptotic factors, gut microbiota, and gut tight junction proteins among three groups of mice. The inter-group comparison was conducted using a t-test and one-way analysis of variance.Results:The rifaximin-treated group had significantly improved liver histopathology. The serological levels of alanine aminotransferase and aspartate aminotransferase were (559.04±89.42) U/L and (676.90±106.25) U/L, respectively, which were significantly lower than those in the PA-HSOS model group [(846.05±148.46) U/L and (953.87±58.10) U/L, P<0.05], and were accompanied by lower levels of apoptotic cells and inflammatory factors. Additionally, the rifaximin-treated mice group gut microbiota had higher diversity compared with the PA-HSOS group ( P<0.05), and the Shannon index was 7.77±0.10 and 7.16±0.07, respectively, indicating apparent differences in microbiota among different groups. The abundance of Firmicutes in the rifaximin group was 39.58%±0.56%, which was significantly higher than that in the model group (24.25%±0.64%, P<0.05), while the abundance of Bacteroidetes was 54.7%±0.41%, which was significantly lower than that in the model group (70.92%±0.49%, P<0.05). Simultaneously, the expressions of gut tight junction proteins ZO-1 and Occludin showed an upward trend and validated transcription levels compared to the model group following rifaximin intervention ( P<0.05). Conclusion:Rifaximin can alleviate monocrotaline-induced hepatic sinusoidal obstruction syndrome in mice, and its mechanism may be via gut microbiota regulation, which in turn plays a role in improving intestinal barrier function.

Objective:To develop and explore the clinical value of a nomogram model for the preoperative diagnosis of proliferative hepatocellular carcinoma (HCC) based on gadoxetate disodium (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI).Methods:The preoperative Gd-EOB-DTPA-enhanced MRI data and clinical pathological data of patients with pathologically confirmed proliferative (178 cases) and non-proliferative type HCC (378 cases) from September 2017 to November 2022 were retrospectively collected. The MRI features and clinicopathological features of proliferative and non-proliferative type HCC were evaluated. Multivariate logistic regression analysis was used to determine the independent predictive factors of proliferative-type HCC. The nomogram prediction model was constructed using R software. The receiver operating characteristic curve (ROC) was used to evaluate its diagnostic efficacy. The calibration curve and decision curve analysis (DCA) were drawn to evaluate the calibration performance and clinical application value of the nomogram model. The optimal threshold for distinguishing high-risk from low-risk was determined using the Youden index. The survival prognosis of proliferative and non-proliferative type HCC was analyzed and compared using the Kaplan-Meier survival curve and the log-rank test. The measurement data were analyzed using the independent sample t-test or the Mann-Whitney U test. The count data were compared using the χ2 test. Results:There were statistically significant differences in alpha-fetoprotein (AFP) levels ( χ2=17.244, P<0.001), tumor morphology ( χ2=13.669, P<0.001), intratumoral fatty degeneration ( χ2=10.495, P=0.001), abnormal enhancement of peritumoral abnormalities during arterial phase ( χ2=37.662, P<0.001), tumor capsule ( χ2=23.961, P<0.001), intratumoral necrosis ( χ2=77.184, P<0.001), intratumoral hemorrhage ( χ2=4.892, P=0.027), peritumoral hypointense in hepatobiliary phase ( χ2=47.675, P<0.001), rim arterial phase hyperenhancement ( χ2=115.976, P<0.001), intratumoral artery ( χ2=15.528, P<0.001) and intravenous tumor thrombus ( χ2=10.532, P=0.001) between proliferative and non-proliferative type HCC groups. Multivariate logistic regression analysis showed that AFP>200 μg/L ( OR=1.561, P=0.044), no intratumoral fatty degeneration ( OR=1.947, P=0.033), intratumoral necrosis ( OR=2.084, P=0.003), peritumoral hypointensity in the hepatobiliary phase ( OR=2.314, P=0.001), and annular hyperenhancement in the arterial phase ( OR=5.557, P<0.001) were independent predictors for preoperative diagnosis of proliferative-type HCC. A nomogram model for preoperative prediction of proliferative type HCC was constructed based on the independent predictors. The area under the ROC curve model for predicting proliferative-type HCC was 0.772 (95% CI: 0.735-0.807), with a sensitivity of 69.1% and a specificity of 75.4%. The calibration curve and DCA curve showed superior calibration performance and clinical applicability of the nomogram model. The Kaplan-Meier curve showed that the recurrence free survival rate after liver resection was significantly lower in patients with proliferative-type HCC than that of non-proliferative-type HCC ( P<0.001), and the high-risk group was significantly lower than the low-risk group ( P<0.001). Conclusions:The construction of a nomogram model based on Gd-EOB-DTPA-enhanced MRI features combined with AFP >200μg/L can accurately diagnose proliferative-type HCC and predict its preoperative prognosis.